Amelotex - instructions for use, dose, side effects, contraindications

AMELOTEKS® is a non-steroidal anti-inflammatory drug with analgesic, anti-inflammatory and antipyretic effects. The anti-inflammatory effect is associated with inhibition of the enzymatic activity of cyclooxygenase-2 (COX-2), which participates in the biosynthesis of prostaglandins in the inflammatory region. Less meloxicam acts on cyclooxygenase-1 (COX-1), involved in the synthesis of prostaglandin, which protects the mucous membrane of the gastrointestinal tract and takes part in the regulation of blood flow in the kidneys.

Suppresses the synthesis of prostaglandins in the inflammation region to a greater extent than in the gastric mucosa or kidneys, which is associated with a relatively selective inhibition of COX-2.

Pharmacokinetics:

Absolute bioavailability of meloxicam is 89%.

The maximum concentration of the drug in plasma in period of sustainable state of pharmacokinetics is achieved in about 5 hours after application of the drug. With a single dose of the drug, the maximum maximum concentration in the blood plasma is reached within 5-6 hours. When using the drug inside at doses of 7.5 mg and 15 mg of its concentration are proportional to the doses. Equilibrium concentrations are achieved within 3-5 days. Range of differences between FROM_m_Oh and C_min after reception once a day is relatively small and is when using a dose of 15 mg - 0.8 - 2.1 μg / ml, (values, respectively, are given C_min and C_max).

Distribution

Binding to plasma proteins is more than 99%. Meloksikam penetrates through the histohematological barriers, the concentration in the synovial fluid reaches 50% of the maximum concentration of the drug in the plasma. The volume of distribution is low, an average of 11 liters. Individual fluctuations - 30-40%.

Metabolism

Almost completely metabolized in the liver with the formation of four pharmacologically inactive derivatives. The main metabolite, 5'-carboxymeloxicam (60% of the dose value), is formed by oxidation of the intermediate metabolite, 5'-hydroxymethylmeloxicam, which is also excreted, but to a lesser degree (9% of the dose value). Research in vitro showed that in this metabolic transformation an important role is played by the isoenzyme CYP 2C9, isozyme has an additional value CYP 3A4. In the formation of the other two metabolites (which constitute, respectively, 16% and 4% of the dose), peroxidase takes part, the activity of which probably varies individually.

Excretion

It is excreted equally through the intestines and kidneys, mainly in the form of metabolites. Through the intestine, less than 5% of the daily dose is excreted in unchanged form, in the unchanged form of the urine the drug is found only in trace amounts. The half-life period (T1 / 2) of meloxicam is 15-20 hours. Plasma clearance is an average of 8 ml / min.

Liver and / or kidney failure

Insufficiency of liver function, as well as renal failure of mild to moderate severity, have no significant effect on the pharmacokinetics of meloxicam. At the terminal stage of renal failure, an increase in the volume of distribution can lead to higher concentrations of free meloxicam, so in these patients the daily dose should not exceed 7.5 mg.

Elderly patients (over 65 years of age)

In elderly patients, the average plasma clearance during the steady state of pharmacokinetics is slightly lower than in young patients.

Indications:

- Osteoarthritis;

- rheumatoid arthritis;

- ankylosing spondylitis (Bekhterev's disease).

It is intended for symptomatic therapy, reducing pain and inflammation at the time of use, the progression of the disease is not affected.

Contraindications:

- Hypersensitivity to the active substance or any auxiliary component of the drug;

- contraindicated in the period after aortocoronary bypass surgery;

- uncompensated heart failure;

- complete or incomplete combination of bronchial asthma, recurrent nasal polyposis and paranasal sinuses and intolerance to acetylsalicylic acid and other non-steroidal anti-inflammatory drugs (including in the anamnesis);

- erosive and ulcerous changes in the mucous membrane of the stomach or duodenum, acute hemorrhagic gastritis, active gastrointestinal bleeding;

- inflammatory bowel disease in the phase of exacerbation (ulcerative colitis, Crohn's disease);

- cerebrovascular bleeding or other bleeding;

- severe hepatic impairment or active liver disease;

- severe renal failure in patients not undergoing dialysis (creatinine clearance (CK) less than 30 ml / min), progressive kidney disease, incl. confirmed hyperkalemia;

- pregnancy, the period of breastfeeding;

- children's age till 15 years.

Suppositories should not be used in patients with any inflammatory diseases of the rectum or anus, or in patients with recent bleeding from the rectum or anus.

Carefully:

To reduce the risk of developing adverse events, the minimum effective dose should be used as short a course as possible with: coronary heart disease, cerebrovascular disease, chronic heart failure, dyslipidemia / hyperlipidemia, diabetes, peripheral arterial diseases, smoking, kidney failure with KK 30-60 ml / min, anamnestic data on the development of ulcerative lesions of the gastrointestinal tract, in the presence of infection Helicobacter pylori, in old age, with the long-term use of non-steroidal anti-inflammatory drugs, frequent use of alcohol, severe somatic diseases,concomitant therapy with the following drugs: anticoagulants (eg, warfarin), antiaggregants (for example acetylsalicylic acid, clopidogrel), oral glucocorticosteroids (for example, prednisolone), selective serotonin reuptake inhibitors (for example, citalopram, fluoxetine, paroxetine, sertraline) (see section "Interaction with other drugs").

Pregnancy and lactation:

AMELOTEX® is contraindicated during pregnancy. Suppressing the synthesis of prostaglandins can have an undesirable effect on the course of pregnancy and fetal development.

It is known that non-steroidal anti-inflammatory drugs penetrate into breast milk, therefore AMELOTEKS® is not recommended for use during breast-feeding.

Dosing and Administration:

Rectally, releasing the suppository from the contoured package, injected deep into the posterior passage. Before using the suppository it is recommended to empty the intestine. Recommended dosing regimen:

Rheumatoid arthritis: 15 mg per day. Depending on the therapeutic effect, the dose can be reduced to 7.5 mg per day.

Osteoarthritis: 7.5 mg per day.If necessary, the dose may be increased to 15 mg per day.

Ankylosing spondylitis: 15 mg per day. Depending on the therapeutic effect, the dose can be reduced to 7.5 mg per day.

Rectal suppositories are recommended to be applied at a dose of 7.5 mg once a day. In more severe cases, it is possible to use suppositories at a dose of 15 mg. Maximum daily dose is not must exceed 15 mg.

The drug should be applied rectally for as short a time as possible, taking into account the summation of the risk of local toxicity and the risk associated with the systemic effect of the drug.

In patients with an increased risk of side effects, as well as in patients with severe renal failure who are on hemodialysis, the dose should not exceed 7.5 mg per day.

Combined application

The total daily dose of meloxicam, used in the form of tablets, suppositories, injections and other dosage forms, should not exceed 15 mg.

Side effects:

The frequency of side effects is given in accordance with the classification of the World Health Organization (WHO): very often (more than 10%), often (1-10%), infrequently (0.1-1%), rarely (0.01-0.1% %), very rarely (less than 0.01%), including individual reports.

From the gastrointestinal tract: often - dyspepsia, incl. nausea, vomiting, abdominal pain, constipation, flatulence, diarrhea; infrequent - transient increase in the activity of "liver" transaminases, hyperbilirubinemia, belching, esophagitis, gastroduodenal ulcer, bleeding from the gastrointestinal tract (including latent), stomatitis; rarely - perforation of the gastrointestinal tract, colitis, hepatitis, gastritis.

From the hematopoiesis: often - anemia; infrequently - a change in the blood formula, incl. leukopenia, thrombocytopenia.

From the skin: often - itching, skin rash; infrequently - hives; rarely - photosensitivity, bullous eruptions, erythema multiforme, incl. Stevens-Johnson syndrome, toxic epidermal necrolysis.

From the respiratory system: rarely - bronchospasm.

From the nervous system: often - dizziness, headache; infrequently - vertigo, noise in the ears, drowsiness; rarely confusion, disorientation, emotional lability.

From the cardiovascular system: often - peripheral edema; infrequently - increased blood pressure, a feeling of palpitations, "tides" of blood to the skin of the face.

From the urinary system: infrequently - hypercreatininaemia and / or increased urea concentration in blood serum; rarely acute renal failure; communication with the drug AMELOTEKS ® is not established - interstitial nephritis, albuminuria, hematuria.

From the sense organs: rarely - conjunctivitis, impaired vision, including blurred vision.

Allergic reactions: rarely - angioedema, anaphylactoid / anaphylactic reactions.

Local reactions with rectal administration: there may be urges for defecation and a feeling of discomfort that pass on their own and do not require the withdrawal of the drug; itching, burning in the perianal area, irritation of the mucous membrane of the rectum.

Overdose:

Symptoms: impaired consciousness, nausea, vomiting, epigastric pain, gastrointestinal bleeding, acute renal failure, hepatic failure, respiratory arrest, asystole.

Treatment: symptomatic therapy. There is no specific antidote. Kolestyramine accelerates the removal of the drug from the body. Forced diuresis, hemodialysis - ineffective due to the high connection of the drug with blood proteins.

Interaction:

When used simultaneously with other non-steroidal anti-inflammatory drugs (as well as with acetylsalicylic acid), the risk of erosive and ulcerative lesions and bleeding from the gastrointestinal tract increases.

When used simultaneously with antihypertensive drugs (for example, beta-blockers, angiotensin converting enzyme (ACE inhibitors), vasodilators, diuretics), it is possible to decrease the effectiveness of the latter, due to the inhibition of prostaglandins with vasodilating properties.

The combined use of NSAIDs and angiotensin II receptor antagonists (as well as ACE inhibitors) enhances the effect of reducing glomerular filtration. In patients with impaired renal function, this can lead to the development of acute renal failure.

When used simultaneously with lithium preparations, lithium can be cumulated by reducing renal excretion and increasing its toxic effect (it is recommended to monitor the concentration of lithium in blood plasma if necessary for such combination therapy).

When used simultaneously with methotrexate, NSAIDs can reduce tubular secretion methotrexate, and thus increase the concentration of methotrexate in the plasma, enhancing its side effect on the hematopoietic system (the risk of anemia and leukopenia, the periodic monitoring of the general blood test is shown). In this regard, in patients receiving high doses of methotrexate (more than 15 mg in week) simultaneous application NSAIDs not recommended. Risk interaction with the simultaneous use of methotrexate and NSAIDs is also possible in patients receiving low doses of methotrexate, especially in patients with impaired renal function. If necessary, combined therapy should monitor the blood formula and kidney function. Care should be taken if the NSAIDs and methotrexate apply simultaneously for 3 days, because the concentration of methotrexate in the plasma may increase and, as a consequence, toxic effects may occur. Simultaneous use of AMELOTEX® did not affect the pharmacokinetics of methotrexate at a dose of 15 mg per week, but it should be taken into account that the hematological toxicity of methotrexate is enhanced by the simultaneous administration of NSAID1.With simultaneous use with diuretics and with cyclosporine, the risk of acute renal failure increases. Patients receiving AMELOTEX® and diuretics should be adequately rehydrated. Before the beginning of treatment it is necessary to study the function of the kidneys.

NSAIDs, acting on renal prostaglandins, can enhance the nephrotoxicity of cyclosporine. In the case of combined therapy, kidney function should be monitored.

With simultaneous use with intrauterine contraceptives, the effectiveness of the latter may be reduced.

When used simultaneously with anticoagulants (heparin, ticlopidine, warfarin), as well as with thrombolytic drugs (streptokinase, fibrinolysin), the risk of bleeding increases (periodic monitoring of blood coagulability indices is necessary).

When used simultaneously with colestyramine, as a result of the binding of the drug AMELOTEKS®, its excretion through the gastrointestinal tract is intensified (see section "Overdose"),

When used simultaneously with selective serotonin reuptake inhibitors, the risk of developing gastrointestinal bleeding increases.

It is impossible to exclude the possibility of interaction with hypoglycemic drugs for oral administration.

Special instructions:

As with other NSAIDs, gastrointestinal bleeding, ulcers and perforations, potentially life-threatening to the patient, can occur during treatment at any time, as in the presence of alarming symptoms or information about serious gastrointestinal complications in the history, and at absence of these signs. Implications of data complications in general serious in the elderly. Caution should be exercised when using AMELOTEX® (as well as with other NSAIDs) in patients with a history of gastrointestinal disease, elderly patients, as well as in patients undergoing anticoagulant therapy. In such patients, the risk of erosive and ulcerative diseases of the gastrointestinal tract is increased. In this case, as well as for the treatment of patients requiring a low dose of acetylsalicylic acid or other drugs that increase gastrointestinal risks, combined therapy with protective medicinal products (such as misoprostol or proton pump inhibitors).

When ulcerative lesions of the gastrointestinal tract or gastrointestinal bleeding occur, treatment with AMELOTEX® should be stopped. Particular attention should be given to patients reporting the development of adverse skin and mucous membrane effects (pruritus, skin rash, hives, photosensitivity). In such cases, the issue of stopping the use of AMELOTEX® should be considered.

NSAIDs inhibit the synthesis of prostaglandins in the kidneys, which are involved in maintaining renal perfusion. The use of NSAIDs in patients with reduced renal blood flow or a reduced volume of circulating blood can lead to decompensation of the secretive renal failure. After the abolition of NSAIDs, the kidney function is usually restored. The elderly are at greatest risk of developing this reaction; patients with dehydration, chronic heart failure, cirrhosis, nephrotic syndrome or kidney disease; patients receiving diuretics, ACE inhibitors, angiotensin II receptor antagonists, as well as patients who underwent serious surgical interventions,leading to hypovolemia. In such patients at the beginning of therapy, diuresis and renal function should be carefully monitored (see section "Interaction with other drugs"),

In patients with renal insufficiency, if creatinine clearance is more than 30 ml / min, dosage adjustment is not required.

Have patients with terminal renal disease deficiency, on hemodialysis, dosage of AMELOTEX® should not exceed 7.5 mg / day.

With persistent and significant increase in the activity of "liver" transaminases and changes in other indicators of liver function, the drug should be discontinued and administered observation of identified laboratory changes. In patients with cirrhosis of the liver in the compensation stage, a reduction in the dose of the drug is not required.

Patients taking both diuretics and AMELOTEX® should take a sufficient amount of fluid.

AMELOTEX®, as well as other non-steroidal anti-inflammatory drugs, can mask the symptoms of infectious diseases.

The use of AMELOTEX®, as well as other drugs that block the synthesis of prostaglandins, can affect fertility,so it is not recommended for women planning a pregnancy.

Effect on the ability to drive transp. cf. and fur:

The use of the drug can cause the emergence of unwanted effects in the form of headaches and dizziness, drowsiness. It should abandon the management of vehicles and maintenance of machines and mechanisms that require concentration of attention.

Form release / dosage:

Suppositories rectal, 7.5 mg and 15 mg.

Packaging:

1 suppository in a contiguous cell package.

1 contour pack together with instructions for use in a pack of cardboard. 3 suppositories in a contour squamous packaging.

1,2,3 or 4 contour packagings together with instructions for use in a pack of cardboard.

5 suppositories in a contiguous cell package.

1 or 2 contour mesh packages together with instructions for use in a pack of cardboard.

Storage conditions:

In a dry place at a temperature of no higher than 25 ° C.

Store in inaccessible to children.

Shelf life:

2 years. Not use at expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-002780

Date of registration:19.12.2014

Expiration Date:19.12.2019

The owner of the registration certificate:FarmSirma Soteks, ZAO FarmSirma Soteks, ZAO Russia

Manufacturer: & nbsp

FARMPROJECT, CJSC Russia

Information update date: & nbsp19.03.2018

Illustrated instructions

Instructions

Ameloteks® (Amelotex®)